The Wales forward missed training on Friday and, although head coach Santiago Solari did not categorically rule him out, featuring versus Rayo looks like a long shot.
"We'll see. It's a matter of rest because it's his ankle," Solari told a news conference.
"We will see how it evolves. We will talk with the doctors and with him and we will think about it."
Bale has scored seven goals in 20 appearances across all competitions for Los Blancos this season.
He was on target in his last Liga outing against Huesca.
Solari may be denied the opportunity to play the Welshman back into peak form as he faces up to another enforced rest.
Fitness struggles have been all too frequent for Bale throughout his time with Madrid, sparking talk of moves elsewhere at regular intervals.
Real have stuck with him, but they could do with seeing him steer clear of the treatment table for a while as they endeavour to salvage a 2018-19 campaign which got off to a rocky start.